Abstract:
A highly selective hydrogenation of 3-keto in steroids to 3-hydroxyl steroids catalyzed by hydroxysteroid dehydrogenases (HSDHs) was demonstrated. The Ct3α-HSDH-catalyzed hydrogenation generated 3α-hydroxyl steroids as the main enantiopure isomers in high yields, while the Ss3β-HSDH catalytic system afforded 3β-hydroxyl steroids in excellent yields. In both catalytic systems, the hydrogenation proceeded regioselectively at 3-keto with 7-, 11-, 17-, and 20-keto almost unreacted, and chemoselectively with the C═C bond and ester group unattacked. Our HSDH-promoted hydrogenation showed advantages like high regio-, chemo-, and enantioselectivity, good yields, mild conditions, a wide substrate scope, and being suitable for gram-scale synthesis. Notably, bioactive molecules like dehydroepiandrosterone, brienolone, and alfaxalone were obtained facilely in high yields via our hydrogenation approach.
摘要:
证明了由羟基类固醇脱氢酶(HSDH)催化的类固醇中的3-酮向3-羟基类固醇的高度选择性氢化。Ct3α-HSDH催化加氢生成3α-羟基甾体作为主要的对映体纯异构体,而Ss3β-HSDH催化体系以优异的产率提供3β-羟基类固醇。在这两种催化体系中,氢化在3-酮与7-,11-,17-,20酮几乎未反应,并且化学选择性地具有C=C键和未攻击的酯基。我们的HSDH促进的氢化显示出诸如高区域,化学-,和对映选择性,良好的产量,温和的条件,广泛的基底范围,适用于克尺度合成。值得注意的是,生物活性分子,如脱氢表雄酮,brienolone,通过我们的氢化方法可以轻松地以高产率获得阿法沙松。